“The rationale for the study was based on preclinical work suggesting that epigenetic modifiers might be able to enhance the efficacy of immune therapies, and this would be particularly important for ‘colder’ tumor types like breast cancer that might not have the same sort of responses that we see in other tumor types,” Dr. Connolly explained in an interview. “The lab work suggested, for example, that the [histone deacetylase] inhibitor entinostat might affect myeloid-derived suppressor and regulatory T cells that might prevent cytotoxic T cells from fighting the cancer.”
There may be other mechanisms for this activity as well, she noted.
The run-in period with entinostat alone allowed collection of pre- and posttreatment biopsies to examine the effects on the tissues, such as whether treatment affects T cells, myeloid-derived suppressor cells, or their pathways, she said.
“We’re seeing [the] same types of toxicities seen with combination immune-oncology strategies, and we’re seeing some tumor responses that are of interest. Now we will delve into the tissue biopsies and blood samples we’ve collected to explore the mechanisms in more detail. In the near future we will open our breast cancer expansion cohort to look in more detail at what these drugs might be doing in breast cancer,” she added.